Foot and Mouth Disease (FMD)
FMD is a highly contagious and economically devastating disease of cloven-hoofed animals (Artiodactyla), affecting domesticated ruminants, pigs and a large number of wildlife species (Alexandersen et al., (2003) Journal of Comparative Pathology 129:1-36) of which the causal agent is Foot-and-Mouth Disease Virus (FMDV).
FMDV is a positive sense, single stranded RNA virus and is the type species of the Aphthovirus genus of the Picornaviridae family. FMDV exists as seven antigenically distinct serotypes namely A, O, C, Asia 1 and South African Territories (SAT) 1, 2 and 3, with numerous subtypes within each serotype. With the exception of New Zealand, outbreaks have been recorded in every livestock-containing region of the world and the disease is currently enzootic in all continents except Australia and North America. Although mortality rates are generally low (less than 5%) in adult animals, the UK 2001 FMD Pan-Asian O outbreak clearly identifies the serious economic consequences associated with the disease, with the cost to the public sector estimated at over 4.5 billion euros and the cost to the private sector at over 7.5 billion euros (Royal Society Report (2002) on Infectious Disease in Livestock-Scientific questions relating to the transmission, prevention and control of epidemic outbreaks of infectious disease in livestock in Great Britain. (2002) Latimer Trend Limited, Cornwall, UK).
FMD is ranked first in the l'Office International des Epizooties (OIE, World Organisation for Animal Health) list of notifiable diseases, which by definition, means that it has the potential for rapid and extensive spread within and between countries. Thus, current intensive farming practices and high stocking densities clearly encourage the rapid spread of such a disease.
FMD is widely distributed throughout the world. Developed regions such as the continents of North and Central America and Antarctica, and countries such as Australia and New Zealand are free from disease while FMD is endemic in many developing countries such as those in sub-Saharan Africa, the Middle East, southern Asia, Southeast Asia and South America. There are also some areas of the world which are normally free from disease, such as Europe where FMD was eradicated in 1989 and where vaccination has ceased since 1991. However, there have been occasional incursions of disease such as the 2001 UK/EIRE/France/Netherlands epidemic due to a PanAsian O strain (Knowles et al., (2001) Veterinary Record. 148. 258-259) and the 2007 UK outbreak of serotype O1 BFS/1967.
Conventional vaccines against FMD consist of whole virus virions that have been chemically inactivated, normally by use of an aziridine such as binary ethyleneimine (BEI). More than a billion doses are used annually worldwide (Rweyemamu and Le Forban (1999) Advances in Virus Research. 53. 111-126) and in many countries have been utilised successfully in controlling the disease.
Capsid Stability
Conventional formulated FMD vaccines need to be stored at 4° C. and have an expected shelf life of at most 12-18 months.
Capsid stability is disrupted by both pH and temperature with temperatures above 56° C. and a pH below 6.8 or above 9.0 believed to result in inactivation of the virus due to dissociation of the intact 146S particle into 12S particles.
A problem associated with current FMD vaccines is thus their limited thermostability and their reliance on a good cold-chain along with appropriate diluents and excipients. There is therefore a need for improved FMD vaccines.